New Studies on Pediatric Liver Diseases

At this year's Liver Meeting, the 69th annual meeting of the American Association for the Study of Liver Diseases, investigators highlighted progress in understanding the incidence, mechanisms, diagnostic approaches, and outcomes of two common liver disorders of children and adolescents—fatty liver and biliary atresia. This article highlights some of the new concepts and approaches that emerged from the relevant presentations.

Screening Strategies for Fatty Liver

There are two suggested strategies to screen for nonalcoholic fatty liver disease (NAFLD) in obese and overweight children with risk factors, which come from separate North American and European medical societies. Statements from the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition [NASPGHAN]^[1] and the American Academy of Pediatrics^[2] recommend screening for NAFLD using serum alanine aminotransferase (ALT) levels, whereas the European Society for Paediatric Gastroenterology Hepatology and Nutrition [ESPGHAN]^[3] and the European Association for the Study of the Liver^[4] recommend using both ALT levels and abdominal ultrasound.

Ezaizi and colleagues^[5] assessed the prevalence of NAFLD in 344 consecutive overweight and obese children seen at a multidisciplinary weight management program using these two disparate screening strategies. Each child underwent a liver ultrasound and had an ALT level measured at the time of their first visit.

NAFLD was present on ultrasound in 53%. The authors compared the NASPGHAN strategy of using an ALT level >2 times the gender-specific cutoff (upper limits of normal in children are 22 U/L for girls and 26 U/L for boys), against the ESPGHAN strategy of using an elevated ALT level (>45 U/L) and a fatty liver noted on ultrasound. The prevalence of NAFLD was 26% based on the NASPGHAN strategy and 59% based on the ESPGHAN strategy. ALT was >2 times the gender-specific cutoff in only 26% of children with evidence of fatty liver on ultrasound. Therefore, by relying on the NASPGHAN strategy, NAFLD would have been missed in 32% of obese children.

Further, univariable analysis indicated that children with NAFLD on ultrasound and low ALT levels were less likely to have metabolic syndrome and insulin resistance, as indicated by lower fasting insulin levels and homeostatic model assessment of insulin resistance. Multivariable analysis confirmed that the absence of metabolic syndrome was associated with increased likelihood of having a normal ALT level in obese children with NAFLD on ultrasound. In addition, patients without hypertriglyceridemia were 2.5 times more likely to have a normal ALT level than those with hypertriglyceridemia.

The investigators concluded that screening for NAFLD in real-life clinical settings should rely on both liver ultrasound and ALT values, and perhaps other markers of metabolic syndrome, to increase the identification rate of this rapidly increasing chronic liver disease.

Controlled Attenuation Parameter (CAP) vs Liver Biopsy to Assess Steatosis

CAP is a noninvasive method to detect and quantify steatosis via radiofrequency ultrasound signals acquired by transient elastography (FibroScan; Echosens, Paris, France).

Nguyen and colleagues^[6] assessed steatosis by CAP, comparing its results with those of steatosis on liver biopsy in children and young adults with NAFLD. Thirty-six patients (mean age, 16 years) had biopsies confirming NAFLD. The median ALT levels, obtained on the day of CAP assessment for 55% of patients and ≤5 weeks from CAP in 85%, were 150, 101, and 137 for patients with mild, moderate, and marked steatosis, respectively. CAP measurements were obtained ≤9 months from biopsy and the majority within 2 months; the optimal CAP cut-point to predict steatosis was 225 dB/m. In these patients preselected for having a high likelihood of NAFLD, although all CAP values were above the "normal" cutoff, there was no difference in mean CAP by steatosis severity.

The investigators concluded that, although CAP is effective for detecting steatosis in the general pediatric population, there was no significant difference in CAP measurements by steatosis grade in children and young adults with biopsy-proven NAFLD.

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